Sleep in Infants and Children with Prenatal Alcohol Exposure

Prenatal exposure to alcohol can result in a range of neurobehavioral impairments and physical abnormalities. The term “fetal alcohol spectrum disorders (FASD)” encompasses the outcomes of prenatal alcohol exposure (PAE), the most severe of which is fetal alcohol syndrome. These effects have lifelong consequences, placing a significant burden on affected individuals, caregivers, and communities. Caregivers of affected children often report that their child has sleep problems, and many symptoms of sleep deprivation overlap with the cognitive and behavioral deficits characteristic of FASD. Alcohol‐exposed infants and children demonstrate poor sleep quality based on measures of electroencephalography, actigraphy, and questionnaires. These sleep studies indicate a common theme of disrupted sleep pattern, more frequent awakenings, and reduced total sleep time. However, relatively little is known about circadian rhythm disruption and the neurobehavioral correlates of sleep disturbance in individuals with PAE. Furthermore, there is limited information available to healthcare providers about identification and treatment of sleep disorders in patients with FASD. This review consolidates the findings from studies of infant and pediatric sleep in this population, providing an overview of typical sleep characteristics, neurobehavioral correlates of sleep disruption, and potential avenues for intervention in the context of PAE.     

Toward a Neurobehavioral Profile of Fetal Alcohol Spectrum Disorders

Background: A primary goal of recent research is the development of neurobehavioral profiles that specifically define fetal alcohol spectrum disorders (FASD), which may assist differential diagnosis or improve treatment. In the current study, we define a preliminary profile using neuropsychological data from a multisite study. Methods: Data were collected using a broad neurobehavioral protocol from 2 sites of a multisite study of FASD. Subjects were children with heavy prenatal alcohol exposure and unexposed controls. The alcohol‐exposed group included children with and without fetal alcohol syndrome (FAS). From 547 neuropsychological variables, 22 variables were selected for analysis based on their ability to distinguish children with heavy prenatal alcohol exposure from nonexposed controls. These data were analyzed using latent profile analysis (LPA). Results: The results indicated that a 2‐class model best fit the data. The resulting profile was successful at distinguishing subjects with FAS from nonexposed controls without FAS with 92% overall accuracy; 87.8% of FAS cases and 95.7% of controls were correctly classified. The same analysis was repeated with children with heavy prenatal alcohol exposure but without FAS and nonexposed controls with similar results. The overall accuracy was 84.7%; 68.4% of alcohol‐exposed cases and 95% of controls were correctly classified. In both analyses, the profile based on neuropsychological variables was more successful at distinguishing the groups than was IQ alone. Conclusions: We used data from 2 sites of a multisite study and a broad neuropsychological test battery to determine a profile that could be used to accurately identify children affected by prenatal alcohol exposure. Results indicated that measures of executive function and spatial processing are especially sensitive to prenatal alcohol exposure.     

Neurobehavioral characteristics of children with fetal alcohol spectrum disorders in communities from Italy: Preliminary results

BACKGROUND: There has been considerable effort expended on defining neurobehavioral characteristics of children with fetal alcohol spectrum disorders (FASD). Children with FASD display a range of cognitive deficits and behavioral problems. In this article, we report on the neurobehavioral characteristics of children with FASD in selected communities in Italy. It was expected that both inattentive and hyperactive/impulsive characteristics would discriminate children with FASD from controls and that the groups would also differ on intellectual functioning, language comprehension, and academic skills. METHODS: Eighty-two children, 22 diagnosed with FASD and 60 control children, participated in this study. The children were administered tests of nonverbal reasoning, language comprehension, academic achievement, and behavior. RESULTS: On tests of nonverbal reasoning and language comprehension, the FASD group earned lower scores than did controls. Moreover, on a test of academic achievement the FASD group scored lower. When comparing these 2 groups on disruptive behavioral symptomatology, similar results were obtained, the FASD group showing greater attentional difficulties and hyperactivity/impulsivity behaviors and more overall behavioral problems. Stepwise logistic regression analysis showed that a model containing inattention and error scores on the language comprehension task correctly classified 85% of the participants. Compared with the control group, a significantly greater proportion of children with FASD met the Diagnostic and Statistical Manual of Mental Disorders-fourth edition (DSM-IV) criteria of ADD, inattentive type, as reported by teachers. In contrast, hyperactive symptoms among children with FASD were comparable with the control group. Teachers rated children with FASD as having more inattentive behaviors and as performing lower in academic skills than controls. The association between reported hyperactivity symptoms and achievement scores was nonsignificant for both language and math scores, suggesting that it is not the hyperactivity causing problems, but the child's inattention. CONCLUSIONS: This research indicates that a nonclinic-referred sample of Italian children with FASD display a profile of neurobehavioral functioning consistent with that reported by other researchers. Furthermore, the neurobehavioral characteristic most identified with children diagnosed with FASD was inattention followed by hyperactivity.     

Fetal Cerebral Circulation as Target of Maternal Alcohol Consumption

Alcohol (ethanol [EtOH]) is one of the most widely used psychoactive substances worldwide. Alcohol consumption during pregnancy may result in a wide range of morphological and neurodevelopmental abnormalities termed fetal alcohol spectrum disorders (FASD), with the most severe cases diagnosed as fetal alcohol syndrome (FAS). FAS and FASD are not readily curable and currently represent the leading preventable causes of birth defect and neurodevelopmental delay in the United States. The etiology of FAS/FASD remains poorly understood. This review focuses on the effects of prenatal alcohol exposure (PAE) on fetal cerebrovascular function. A brief introduction to the epidemiology of alcohol consumption and the developmental characteristics of fetal cerebral circulation is followed by several sections that discuss current evidence documenting alcohol‐driven alterations of fetal cerebral blood flow, artery function, and microvessel networks. The material offers mechanistic insights at the vascular level itself into the pathophysiology of PAE.     

Neuropsychological study of FASD in a sample of American Indian children: processing simple versus complex information

Background: Although a large body of literature exists on cognitive functioning in alcohol‐exposed children, it is unclear if there is a signature neuropsychological profile in children with Fetal Alcohol Spectrum Disorders (FASD). This study assesses cognitive functioning in children with FASD from several American Indian reservations in the Northern Plains States, and it applies a hierarchical model of simple versus complex information processing to further examine cognitive function. We hypothesized that complex tests would discriminate between children with FASD and culturally similar controls, while children with FASD would perform similar to controls on relatively simple tests. Methods: Our sample includes 32 control children and 24 children with a form of FASD [fetal alcohol syndrome (FAS) = 10, partial fetal alcohol syndrome (PFAS) = 14]. The test battery measures general cognitive ability, verbal fluency, executive functioning, memory, and fine‐motor skills. Results: Many of the neuropsychological tests produced results consistent with a hierarchical model of simple versus complex processing. The complexity of the tests was determined “a priori” based on the number of cognitive processes involved in them. Multidimensional scaling was used to statistically analyze the accuracy of classifying the neurocognitive tests into a simple versus complex dichotomy. Hierarchical logistic regression models were then used to define the contribution made by complex versus simple tests in predicting the significant differences between children with FASD and controls. Complex test items discriminated better than simple test items. The tests that conformed well to the model were the Verbal Fluency, Progressive Planning Test (PPT), the Lhermitte memory tasks, and the Grooved Pegboard Test (GPT). The FASD‐grouped children, when compared with controls, demonstrated impaired performance on letter fluency, while their performance was similar on category fluency. On the more complex PPT trials (problems 5 to 8), as well as the Lhermitte logical tasks, the FASD group performed the worst. Conclusions: The differential performance between children with FASD and controls was evident across various neuropsychological measures. The children with FASD performed significantly more poorly on the complex tasks than did the controls. The identification of a neurobehavioral profile in children with prenatal alcohol exposure will help clinicians identify and diagnose children with FASD.     

Comparison of motor delays in young children with fetal alcohol syndrome to those with prenatal alcohol exposure and with no prenatal alcohol exposure

BACKGROUND: Researchers are increasingly considering the importance of motor functioning of children with fetal alcohol spectrum disorder (FASD). The purpose of this study was to assess the motor development of young children with fetal alcohol syndrome (FAS) to determine the presence and degree of delay in their motor skills and to compare their motor development with that of matched children without FAS. METHODS: The motor development of 14 children ages 20 to 68 months identified with FAS was assessed using the Vineland Adaptive Behavior Scales (VABS). In addition, 2 comparison groups were utilized. Eleven of the children with FAS were matched for chronological age, gender, ethnicity, and communication age to: (1) 11 children with prenatal alcohol exposure who did not have FAS and (2) 11 matched children without any reported prenatal alcohol exposure. The motor scores on the VABS were compared among the 3 groups. RESULTS: Most of the young children with FAS in this study showed clinically important delays in their motor development as measured on the VABS Motor Domain, and their fine motor skills were significantly more delayed than their gross motor skills. In the group comparisons, the young children with FAS had significantly lower Motor Domain standard (MotorSS) scores than the children not exposed to alcohol prenatally. They also had significantly lower Fine Motor Developmental Quotients than the children in both the other groups. No significant group differences were found in gross motor scores. For MotorSS scores and Fine Motor Developmental Quotients, the means and standard errors indicated a continuum in the scores from FAS to prenatal alcohol exposure to nonexposure. CONCLUSIONS: These findings strongly suggest that all young children with FAS should receive complete developmental evaluations that include assessment of their motor functioning, to identify problem areas and provide access to developmental intervention programs that target deficit areas such as fine motor skills. Fine motor delays in children with FAS may be related to specific neurobehavioral deficits that affect fine motor skills. The findings support the concept of an FASD continuum in some areas of motor development.     

Congenital Heart Defects and Fetal Alcohol Spectrum Disorders

Objective. Review of the prevalence of congenital heart defects (CHD) and fetal alcohol spectrum disorder (FASD). Design. We conducted a search of the Medline and Pubmed databases to identify papers reporting the association. We then searched the reference lists of the papers and reference books for additional sources. Results. We found 29 studies that met our inclusion criteria. In the 12 case series studies of subjects with FASD, the proportion of cases with a CHD (atrial [ASD] and ventricular [VSD] septal defects, other defects, or unspecified CHD) ranged from 33% to 100%. From the 14 retrospective studies, the rate of septal defects was 21%, other structural defects 6% and unspecified defects was 12%. For the 2 case–control studies, the odds of CHD ranged from 1.0 (subjects with fetal alcohol effect) to 18.0 (subjects with fetal alcohol syndrome). In the 1 prospective study of CHD the OR for a child to have CHD and FASD was 1.0. Key Conclusion. Pediatric cardiologists may have frequent contact with children with FASD and increased levels of attention to prenatal alcohol exposure as a potential etiology of CHD is indicated.     

The Remarkably High Prevalence of Epilepsy and Seizure History in Fetal Alcohol Spectrum Disorders

Background: Fetal alcohol spectrum disorder (FASD) is the umbrella term that describes the range of adverse developmental outcomes that may occur in the offspring of mothers who drink alcohol during pregnancy. FASD is associated with several comorbidities including epilepsy. The objective of the study was to evaluate the prevalence of epilepsy or a history of seizures in subjects with FASD and the contribution of relevant risk factors. Methods: A retrospective chart review was conducted on all active charts (N = 1063) at two FASD clinics. After exclusion of subjects without a confirmed diagnosis, a total of 425 subjects between the ages of 2–49 were included in the analysis. The relationships between FASD diagnosis and other risk factors for co‐occurrence of epilepsy or a seizure disorder (e.g., extent of exposure to alcohol and other drugs, type of birth, and trauma) were examined using chi‐square and multivariate multinomial logistic regression. Results: Twenty‐five (5.9%) individuals in the study population had a confirmed diagnosis of epilepsy, and 50 (11.8%) had at least one documented seizure episode, yielding an overall prevalence of 17.7% in this population. Importantly, a history of epilepsy or seizures was not different across the three diagnostic subgroups. In those subjects with available maternal drinking histories, first trimester exposure or drinking throughout all three trimesters were the predominant forms of fetal exposure. None of the other risk factors were associated with a greater prevalence of epilepsy or seizures. Conclusions: There is a remarkably high prevalence of epilepsy/seizures in the FASD population.     

Magnetic Resonance Imaging Outcomes From a Comprehensive Magnetic Resonance Study of Children With Fetal Alcohol Spectrum Disorders

Background: Magnetic resonance (MR) technology offers noninvasive methods for in vivo assessment of neuroabnormalities. Methods: A comprehensive neuropsychological/psychiatric battery, coupled with MR imaging, (MRI), MR spectroscopy (MRS), and functional MRI (fMRI) assessments, were administered to children with fetal alcohol spectrum disorders (FASD) to determine if global and/or focal abnormalities could be identified, and distinguish diagnostic subclassifications across the spectrum. The 4 study groups included: (i) fetal alcohol syndrome (FAS)/partial FAS (PFAS); (ii) static encephalopathy/alcohol exposed (SE/AE); (iii) neurobehavioral disorder/alcohol exposed (ND/AE) as diagnosed with the FASD 4‐Digit Code; and (iv) healthy peers with no prenatal alcohol exposure. Presented here are the MRI assessments that were used to compare the sizes of brain regions between the 4 groups. The neuropsychological/behavioral, MRS, and fMRI outcomes are reported separately. Results: Progressing across the 4 study groups from Controls to ND/AE to SE/AE to FAS/PFAS, the mean absolute size of the total brain, frontal lobe, caudate, putamen, hippocampus, cerebellar vermis, and corpus callosum length decreased incrementally and significantly. The FAS/PFAS group (the only group with the 4‐Digit FAS facial phenotype) had disproportionately smaller frontal lobes relative to all other groups. The FAS/PFAS and SE/AE groups [the 2 groups with the most severe central nervous system (CNS) dysfunction] had disproportionately smaller caudate regions relative to the ND/AE and Control groups. The prevalence of subjects in the FAS/PFAS, SE/AE, and ND/AE groups that had 1 or more brain regions, 2 or more SDs below the mean size observed in the Control group was 78, 58, and 43%, respectively. Significant correlations were observed between size of brain regions and level of prenatal alcohol exposure, magnitude of FAS facial phenotype, and level of CNS dysfunction. Conclusions: Magnetic resonance imaging provided further validation that ND/AE, SE/AE, and FAS/PFAS as defined by the FASD 4‐Digit Code are 3 clinically distinct and increasingly more affected diagnostic subclassifications under the umbrella of FASD. Neurostructural abnormalities are present across the spectrum. MRI could importantly augment diagnosis of conditions under the umbrella of FASD, once population‐based norms for structural development of the human brain are established.     

The Genetics of Fetal Alcohol Spectrum Disorders

The term “fetal alcohol spectrum disorders” (FASD) defines the full range of ethanol (EtOH)‐induced birth defects. Numerous variables influence the phenotypic outcomes of embryonic EtOH exposure. Among these variables, genetics appears to play an important role, yet our understanding of the genetic predisposition to FASD is still in its infancy. We review the current literature that relates to the genetics of FASD susceptibility and gene–EtOH interactions. Where possible, we comment on potential mechanisms of reported gene–EtOH interactions. Early indications of genetic sensitivity to FASD came from human and animal studies using twins or inbred strains, respectively. These analyses prompted searches for susceptibility loci involved in EtOH metabolism and analyses of candidate loci, based on phenotypes observed in FASD. More recently, genetic screens in animal models have provided an additional insight into the genetics of FASD. Understanding FASD requires that we understand the many factors influencing phenotypic outcome following embryonic EtOH exposure. We are gaining ground on understanding some of the genetics behind FASD, yet much work remains to be carried out. Coordinated analyses using human patients and animal models are likely to be highly fruitful in uncovering the genetics behind FASD.     

Alcohol‐Induced Developmental Origins of Adult‐Onset Diseases

Fetal alcohol exposure may impair growth, development, and function of multiple organ systems and is encompassed by the term fetal alcohol spectrum disorders (FASD). Research has so far focused on the mechanisms, prevention, and diagnosis of FASD, while the risk for adult‐onset chronic diseases in individuals exposed to alcohol in utero is not well explored. David Barker's hypothesis on Developmental Origins of Health and Disease (DOHaD) suggests that insults to the milieu of the developing fetus program it for adult development of chronic diseases. In the 25 years since the introduction of this hypothesis, epidemiological and animal model studies have made significant advancements in identifying in utero developmental origins of chronic adult‐onset diseases affecting cardiovascular, endocrine, musculoskeletal, and psychobehavioral systems. Teratogen exposure is an established programming agent for adult diseases, and recent studies suggest that prenatal alcohol exposure correlates with adult onset of neurobehavioral deficits, cardiovascular disease, endocrine dysfunction, and nutrient homeostasis instability, warranting additional investigation of alcohol‐induced DOHaD, as well as patient follow‐up well into adulthood for affected individuals. In utero epigenetic alterations during critical periods of methylation are a key potential mechanism for programming and susceptibility of adult‐onset chronic diseases, with imprinted genes affecting metabolism being critical targets. Additional studies in epidemiology, phenotypic characterization in response to timing, dose, and duration of exposure, as well as elucidation of mechanisms underlying FASD‐DOHaD inter relation, are thus needed to clinically define chronic disease associated with prenatal alcohol exposure. These studies are critical to establish interventional strategies that decrease incidence of these adult‐onset diseases and promote healthier aging among individuals affected with FASD.     

Brain metabolic alterations in adolescents and young adults with fetal alcohol spectrum disorders

BACKGROUND: Prenatal alcohol exposure affects brain structure and function. This study examined brain metabolism using magnetic resonance spectroscopy (MRS) and searched for regions of specific vulnerability in adolescents and young adults prenatally exposed to alcohol. METHODS: Ten adolescents and young adults with confirmed heavy prenatal alcohol exposure and a diagnosis within the fetal alcohol spectrum disorders (FASD) were included. Three of them had fetal alcohol syndrome (FAS), 3 had partial FAS (PFAS), and 4 had alcohol-related neurobehavioral disorder (ARND). The control group consisted of 10 adolescents matched for age, sex, head circumference, handedness, and body mass. Exclusionary criteria were learning disorders and prenatal alcohol exposure. Three-dimensional (1)H magnetic resonance spectroscopic imaging ((1)H MRSI) was performed in the cerebrum and cerebellum. Metabolite ratios N-acetylaspartate/choline (NAA/Cho), NAA/creatine (Cr) and Cho/Cr, and absolute metabolite intensities were calculated for several anatomic regions. RESULTS: In patients with FASD, lower NAA/Cho and/or NAA/Cr compared with controls were found in parietal and frontal cortices, frontal white matter, corpus callosum, thalamus, and cerebellar dentate nucleus. There was an increase in the absolute intensity of the glial markers Cho and Cr but no change in the neuronal marker NAA. CONCLUSIONS: Our results suggest that prenatal alcohol exposure alters brain metabolism in a long-standing or permanent manner in multiple brain areas. These changes are in accordance with previous findings from structural and functional studies. Metabolic alterations represent changes in the glial cell pool rather than in the neurons.     

A Systematic Review of Interventions to Improve Mental Health and Substance Use Outcomes for Individuals with Prenatal Alcohol Exposure and Fetal Alcohol Spectrum Disorder

Individuals with fetal alcohol spectrum disorder (FASD) experience remarkably high rates of mental health and substance use challenges, beginning early in life and extending throughout adulthood. Proactive intervention can help to mitigate some of these negative experiences. Although the literature on FASD intervention is growing, there is currently a lack of consolidated evidence on interventions that may improve mental health and substance use outcomes in this population. Informed by a life course perspective, we undertook a systematic review of the literature to identify interventions that improve mental wellness through all developmental stages for people with prenatal alcohol exposure (PAE) and FASD. A total of 33 articles were identified, most of which were focused on building skills or strategies that underlie the well-being of children with PAE and FASD and their families. Other interventions were geared toward supporting child and family wellness and responding to risk or reducing harm. There was a notable lack of interventions that directly targeted mental health and substance use challenges, and a major gap was also noted in terms of interventions for adolescents and adults. Combined, these studies provide preliminary and emerging evidence for a range of intervention approaches that may support positive outcomes for individuals with FASD across the life course.     

The Impact of Maternal Age on the Effects of Prenatal Alcohol Exposure on Attention

Background: Prenatal exposure to alcohol has a variety of morphologic and neurobehavioral consequences, yet more than 10% of women continue to drink during pregnancy, placing their offspring at risk for fetal alcohol spectrum disorders (FASD). Identification of at‐risk pregnancies has been difficult, in part, because the presence and severity of FASD are influenced by factors beyond the pattern of alcohol consumption. Establishing maternal characteristics, such as maternal age, that increase the risk of FASD is critical for targeted pregnancy intervention. Methods: We examined the moderating effect of maternal age on measures of attention in 462 children from a longitudinal cohort born to women with known alcohol consumption levels (absolute ounces of alcohol per day at conception) who were recruited during pregnancy. Analyses examined the impact of binge drinking, as average ounces of absolute alcohol per drinking day. Smoking and use of cocaine, marijuana, and opiates were also assessed. At 7 years of age, the children completed the Continuous Performance Test, and their teachers completed the Achenbach Teacher Report Form. Results: After controlling for covariates, stepwise multiple regression analyses revealed a negative relation between levels of prenatal binge drinking and several measures of attention. The interaction between alcohol consumption and maternal age was also significant, indicating that the impact of maternal binge drinking during pregnancy on attention was greater among children born to older drinking mothers. Conclusion: These findings are consistent with previous findings that children born to older alcohol‐using women have more deleterious effects of prenatal alcohol exposure on other neurobehavioral outcomes.     

Experiences of Children with Fetal Alcohol Spectrum Disorder and Their Families: A Critical Review

Evidence suggests that children with fetal alcohol spectrum disorder (FASD) experience challenges across many areas of their daily lives and often require interprofessional supports. Recent studies have emphasized the need for an integrated system of care for children with FASD, incorporating medical, allied health, and education services, to facilitate open communication and support for the complex needs that many children experience. To develop such a system of care, it is important to first understand the impact of FASD on children’s functioning during daily activities in different environmental contexts. A critical review of existing research was conducted using a critical interpretive synthesis approach. Results revealed that while many studies discussed impacts at the body functions and structures level of children with FASD, they often did not consider the activity, participation, and environmental factors also contributing to the daily functioning of this population. Several studies discussed caregiver experiences and challenges raising a child with FASD; however, no studies investigated the lived experiences relating to impacts across activities and environments from children’s perspectives. In addition, the focus on deficits overshadowed investigation into the strengths of children with FASD, leaving a gap in the picture of their daily lives. Further research is required to determine the strengths that children with FASD demonstrate and the challenges impacting their daily functioning within different environmental contexts. Insights gleaned from such research would support intervention practices to become more holistic and interprofessional.     

Prenatal alcohol exposure affects frontal-striatal BOLD response during inhibitory control

BACKGROUND: Prenatal alcohol exposure can lead to widespread cognitive impairment and behavioral dysregulation, including deficits in attention and response inhibition. This study characterized the neural substrates underlying the disinhibited behavioral profile of individuals with fetal alcohol spectrum disorders (FASD). METHODS: Children and adolescents (ages 8-18) with (n=13) and without (n=9) histories of heavy prenatal alcohol exposure underwent functional magnetic resonance imaging while performing a response inhibition (go/no-go) task. RESULTS: Despite similar task performance (mean response latency, performance accuracy, and signal detection), blood oxygen level-dependent (BOLD) response patterns differed by group. Region-of-interest analyses revealed that during portions of the behavioral task that required response inhibition, alcohol-exposed participants showed greater BOLD response across prefrontal cortical regions (including the left medial and right middle frontal gyri), while they showed less right caudate nucleus activation, compared with control participants. CONCLUSIONS: These data provide an account of response inhibition-related brain functioning in youth with FASD. Furthermore, results suggest that the frontal-striatal circuitry thought to mediate inhibitory control is sensitive to alcohol teratogenesis.     

Microstructural Corpus Callosum Anomalies in Children With Prenatal Alcohol Exposure: An Extension of Previous Diffusion Tensor Imaging Findings

Background: Several studies have now shown corpus callosum abnormalities using diffusion tensor imaging (DTI) in children with fetal alcohol spectrum disorders (FASD) in comparison with nonexposed controls. The data suggest that posterior regions of the callosum may be disproportionately affected. The current study builds on previous efforts, including our own work, and moves beyond midline corpus callosum to probe major inter‐hemispheric white matter pathways with an improved DTI tractographic method. This study also expands on our prior work by evaluating a larger sample and by incorporating children with a broader range of clinical effects including full‐criteria fetal alcohol syndrome (FAS). Methods: Participants included 33 children with FASD (8 FAS, 23 partial FAS, 2 static encephalopathy) and 19 nonexposed controls between the ages of 10 and 17 years. Participants underwent DTI scans and intelligence testing. Groups (FASD vs. controls) were compared on fractional anisotropy (FA) and mean diffusivity (MD) in 6 white matter tracts projected through the corpus callosum. Exploratory analyses were also conducted examining the relationships between DTI measures in the corpus callosum and measures of intellectual functioning and facial dysmorphology. Results: In comparison with the control group, the FASD group had significantly lower FA in 3 posterior tracts of the corpus callosum: the posterior mid‐body, the isthmus, and the splenium. A trend‐level finding also suggested lower FA in the genu. Measures of white matter integrity and cognition were correlated and suggest some regional specificity, in that only posterior regions of the corpus callosum were associated with visual‐perceptual skills. Correlations between measures of facial dysmorphology and posterior regions of the corpus callosum were nonsignificant. Conclusions: Consistent with previous DTI studies, these results suggest that microstructural posterior corpus callosum abnormalities are present in children with prenatal alcohol exposure and cognitive impairment. These abnormalities are clinically relevant because they are associated with cognitive deficits and appear to provide evidence of abnormalities associated with prenatal alcohol exposure independent of dysmorphic features. As such, they may yield important diagnostic and prognostic information not provided by the traditional facial characteristics.     

Sensory Processing and Adaptive Behavior Deficits of Children Across the Fetal Alcohol Spectrum Disorder Continuum

Background: Prenatal alcohol exposure can have detrimental effects on a child’s development of adaptive behaviors necessary for success in the areas of academic achievement, socialization, and self‐care. Sensory processing abilities have been found to affect a child’s ability to successfully perform adaptive behaviors. The current study explored whether significant differences in sensory processing abilities, adaptive behavior, and neurocognitive functioning are observed between children diagnosed with partial Fetal Alcohol Syndrome (pFAS), Alcohol‐Related Neurodevelopmental Disorder (ARND), or children who were prenatally exposed to alcohol (PEA), but did not meet criteria for an FASD diagnosis. The influence of IQ on adaptive behavior as well as further exploration of the relationship between sensory processing and adaptive behavior deficits among these children was also examined. Methods: A secondary analysis was conducted on some of the Short Sensory Profile (SSP) scores, Adaptive Behavior Assessment System—Second Edition (ABAS‐II) scores, and Wechsler Intelligence Scale—Fourth Edition/Wechsler Preschool and Primary Scale of Intelligence—Third Edition (WISC‐ IV/WPPSI—III) scores of 46 children between 3 and 14 years of age with pFAS, ARND, or who were PEA. Results: Greater sensory processing deficits were found in children with a diagnosis of pFAS and ARND compared to those in the PEA group. Children with an ARND diagnosis scored significantly worse on measures of adaptive behavior than the PEA group. Children with pFAS scored significantly lower than children with ARND or PEA on perceptual/performance IQ. No correlation was found between IQ scores and adaptive behaviors across the FASD diagnostic categories. A significant positive correlation was found between SSP and ABAS‐II scores. Conclusions: Regardless of the diagnosis received under the FASD umbrella, functional difficulties that could not be observed using traditional measures of intelligence were found, supporting guidelines that a broad range of standardized assessments be included when screening children for FASD.     

Comments and Reflections on Ethics in Screening for Biomarkers of Prenatal Alcohol Exposure

Early identification of and intervention for fetal alcohol spectrum disorder (FASD) has been shown to optimize outcomes for affected individuals. Detecting biomarkers of prenatal alcohol exposure (PAE) in neonates may assist in the identification of children at risk of FASD enabling targeted early interventions. Despite these potential benefits, complicated ethical issues arise in screening for biomarkers of PAE and these must be addressed prior to the implementation of screening programs. Here, we identify and comment, based on a North American perspective, on concerns raised in the current ethical, social, and legal literature related to meconium screening for PAE. Major ethical concerns revolve around the targeting of populations for PAE screening, consent and respect for persons, stigma and participation rates, the cost—benefit analysis of a screening program, consequences of false‐positive and false‐negative test results, confidentiality and appropriate follow‐up to positive screen results, and the use of screen results for criminal prosecution. We identify gaps in the literature on screening for PAE, most notably related to a lack of stakeholder perspectives (e.g., parents, healthcare providers) about screening and the ethical challenges it presents.     

Effect of Alcohol Consumption on CpG Methylation in the Differentially Methylated Regions of H19 and IG-DMR in Male Gametes—Implications for Fetal Alcohol Spectrum Disorders

Background: Exposure to alcohol in utero is the main attributable cause of fetal alcohol spectrum disorders (FASD) which in its most severe form is characterized by irreversible behavioral and cognitive disability. Paternal preconception drinking is not considered to be a significant risk factor, even though animal studies have demonstrated that chronic paternal alcohol consumption has a detrimental effect on the physical and mental development of offspring even in the absence of in utero alcohol exposure. It has been documented that alcohol can reduce the levels and activity of DNA methyltransferases resulting in DNA hypomethylation and that reduced methyltransferase activity can cause activation of normally silenced genes. The aim of this study was to establish a link between alcohol use in men and hypomethylation of paternally imprinted loci in sperm DNA in genomic regions critical for embryonic development, thus providing a mechanism for paternal effects in the aetiology of FASD. Methods: Sperm DNA from male volunteers was bisulfite treated and the methylation patterns of 2 differentially methylated regions (DMRs), H19 and IG‐DMR, analyzed following sequencing of individual clones. The methylation patterns were correlated with the alcohol consumption levels of the volunteer males. Results: There was a pattern of increased demethylation with alcohol consumption at the 2 imprinted loci with a significant difference observed at the IG‐DMR between the nondrinking and heavy alcohol consuming groups. Greater inter‐individual variation in average methylation was observed at the H19 DMR and individual clones were more extensively demethylated than those of the IG‐DMR. CpG site #4 in the IG‐DMR was preferentially demethylated among all individuals and along with the H19 DMR CpG site #7 located within the CTCF binding site 6 showed significant demethylation in the alcohol consuming groups compared with the control group. Conclusion: This study demonstrates a correlation between chronic alcohol use and demethylation of normally hypermethylated imprinted regions in sperm DNA. We hypothesize that, should these epigenetic changes in imprinted genes be transmitted through fertilization, they would alter the critical gene expression dosages required for normal prenatal development resulting in offspring with features of FASD.